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Patients with Rare, Autism-Like Disorder Found to Have Altered Nerve-Fiber Pathways

By MedImaging International staff writers
Posted on 21 Dec 2011

It is still not known what is different in the brains of individuals with autism spectrum disorders (ASDs), but recent findings from genetic and cell studies points to abnormalities in how brain cells (neurons) connect to each other. New research provides visual evidence linking autism with a disorganized structure of brain connections, as well as defects in myelin.

The researchers, led by Mustafa Sahin, MD, PhD, from the department of neurology, Simon Warfield, PhD, director of the Computational Radiology Laboratory, and first author Jurriaan Peters, MD, of both departments at Children’s Hospital Boston (MA, USA), used an innovative magnetic resonance imaging (MRI) technique to image the brains of 40 patients (infants to age 25) with tuberous sclerosis complex and 29 age-matched, healthy controls. Tuberous sclerosis is a rare genetic condition often associated with cognitive and behavioral deficits, including ASDs approximately 50% of the time.

“Patients with tuberous sclerosis can be diagnosed at birth or potentially before birth, because of cardiac tumors that are visible on ultrasound, giving us the opportunity to understand the circuitry of the brain at an early age,” explained Dr. Sahin. “Our ultimate goal is to use imaging in infancy to find which tuberous sclerosis patients are at high risk for autism so we can intervene early. This may have implications for autism in patients without tuberous sclerosis as well.”

The investigators used a comparatively new MRI technique called diffusion tensor imaging (DTI) to track the pathways of nerve fibers by measuring the diffusion of water in the brain. In the January 2011 issue of the journal Academic Radiology, they report findings in the corpus callosum, the brain's largest white-matter structure.

Of the 40 patients with tuberous sclerosis, 24 had clinically significant developmental delays or intellectual disability, and 12 had ASDs. ASDs were diagnosed clinically by a pediatric neurologist, and in most cases, by the Autism Diagnostic Observation Schedule (ADOS).

Typically, compared with controls, patients with tuberous sclerosis had higher radial diffusivity values, a measure of water diffusion out of (perpendicular to) the nerve fibers (axons). Radial diffusivity is an indirect measure of how well insulated the axons are. Having higher radial diffusivity means axons are poorly insulated with myelin, suggesting abnormalities in the white matter (which is partially composed of myelin).

Patients with both tuberous sclerosis and ASDs not only had increased radial diffusivity-- compared with both non-ASD patients and controls --but they also had distinctly disorganized axon pathways.

Axons in the control subjects followed well-defined directions in organized bundles, whereas the ASD patients’ axons tended not to orient together in common directions (referred to in the article as having lower fractional anisotropy). Tuberous sclerosis patients without ASDs showed only slight disorganization compared to controls. “This study shows that we can use diffusion tensor imaging to differentiate tuberous patients with autism from those without autism,” said Dr. Sahin.

“Our advances in imaging and in image analysis are enabling us to identify and quantitatively characterize alterations in brain development that are not readily visible in conventional imaging,'” added Dr. Warfield.

The findings add to earlier human imaging research by Drs. Sahin and Warfield showing similar differences in the brain’s visual cortex, and are consistent with brain MRI scans in older, high-functioning individuals with ASDs, revealing abnormalities in connectivity in the corpus callosum and in areas of brain involved in language and social skills.

The findings are also consistent with studies in Dr. Sahin’s lab using mouse models of tuberous sclerosis. The neurons in these mice grew multiple axons (normal neurons grow just one), causing too many connections being made, and axons originating in the retina failed to land in the appropriate places in the brain and did not respond to navigation cues.

Further studies revealed that the axons in these mice had less myelination, identified the biochemical pathway causing these defects, known as the mTOR pathway, and showed that the pathway and the myelination defects could be reversed in mice with the mTOR-inhibiting drug rapamycin.

Equipped with these data, Dr. Sahin has launched a phase II clinical trial of a rapamycin-like drug called Afinitor (everolimus; formerly RAD001), sponsored by Novartis (Basel, Switzerland), the Tuberous Sclerosis Alliance and Autism Speaks. The trial will enroll 50 patients with TSC to test whether Afinitor improves neurocognition, autism, seizures, and sleep disorders. “Specifically modulating neurocognition with a small molecule is only starting to be done,” stated Dr. Sahin.

“Ultimately, imaging will play a crucial role in identifying who may benefit from treatment, and in seeing the changes in the brain in response to treatment,” concluded Dr. Warfield.

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56 (663.99574279785): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294738547 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

57 (!!!!! 1219.9878692627): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738547 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738547 AND published='1' LIMIT 1

58 (69.141387939453): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738547 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738547 AND published='1' LIMIT 1

59 (137.0906829834): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738547 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738547 AND published='1' LIMIT 1

60 (61.03515625): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738547 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738547 AND published='1' LIMIT 1

61 (92.029571533203): select cover from jos_number where journalid in (5) and cover is not null order by left(issue,2)+right(issue,2)*12 desc limit 1

62 (519.0372467041): SELECT fid FROM jos_deeppockets WHERE id=294738547 AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE id=294738547 AND published='1' LIMIT 1

63 (43.869018554688): SELECT id,name,sponsor_text FROM jos_deeppockets dp left outer join jos_channel_sponsor cs on dp.id=cs.fid WHERE cat=10 AND TYPE='file_folder' AND published=1 AND id=212 ORDER BY `ordering`

64 (43.869018554688): select jos_twitters.link from jos_twitters where cat=10

65 (29.087066650391): select jos_facebook.link from jos_facebook where cat=10

66 (29.802322387695): select jos_google_plus.link from jos_google_plus where cat=10

67 (27.894973754883): select jos_linkedin.link from jos_linkedin where cat=10

68 (30.994415283203): SELECT fid FROM jos_deeppockets WHERE id=294738547 AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE id=294738547 AND published='1' LIMIT 1

69 (30.994415283203): SELECT id,name,sponsor_text FROM jos_deeppockets dp left outer join jos_channel_sponsor cs on dp.id=cs.fid WHERE cat=10 AND TYPE='file_folder' AND published=1 AND id=212 ORDER BY `ordering`

70 (324.01084899902): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294738547 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

71 (301.83792114258): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294738547 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

72 (40.054321289062): SELECT id,name,title FROM jos_deeppockets WHERE cat=10 AND TYPE='file_folder' AND published=1 AND id != 294743300 AND id != 294743301 AND id != 294743302 AND id != 294743303 AND id != 294743304 AND id != 294743305 AND id != 294743306 AND id != 294743307 AND id != 294743308 AND id != 294743309 AND id != 294743310 AND metakey != 'aacc' ORDER BY `ordering`

73 (79.154968261719): SELECT show_live FROM jos_com_show_setting LIMIT 1

74 (32.901763916016): SELECT show_live FROM jos_com_show_setting LIMIT 1

75 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1

76 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

77 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1

78 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

79 (29.087066650391): SELECT show_live FROM jos_com_show_setting LIMIT 1

80 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1

81 (28.848648071289): SELECT show_live FROM jos_com_show_setting LIMIT 1

82 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1

83 (27.179718017578): SELECT show_live FROM jos_com_show_setting LIMIT 1

84 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1

85 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1

86 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1

87 (48.160552978516): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294738547 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

88 (30.994415283203): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294738547 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

89 (32.901763916016): SELECT id,name,title FROM jos_deeppockets WHERE cat=10 AND TYPE='file_folder' AND published=1 AND id != 294743300 AND id != 294743301 AND id != 294743302 AND id != 294743303 AND id != 294743304 AND id != 294743305 AND id != 294743306 AND id != 294743307 AND id != 294743308 AND id != 294743309 AND id != 294743310 AND metakey != 'aacc' ORDER BY `ordering`

90 (48.87580871582): SELECT show_live FROM jos_com_show_setting LIMIT 1

91 (30.040740966797): SELECT show_live FROM jos_com_show_setting LIMIT 1

92 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

93 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

94 (34.093856811523): SELECT show_live FROM jos_com_show_setting LIMIT 1

95 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1

96 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1

97 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

98 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1

99 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

100 (46.968460083008): SELECT show_live FROM jos_com_show_setting LIMIT 1

101 (39.100646972656): SELECT show_live FROM jos_com_show_setting LIMIT 1

102 (29.087066650391): SELECT show_live FROM jos_com_show_setting LIMIT 1

103 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

104 (90.837478637695): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738547 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738547 AND published='1' LIMIT 1

105 (46.968460083008): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738547 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738547 AND published='1' LIMIT 1

106 (49.114227294922): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294738547 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

107 (56.982040405273): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294738547 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

108 (76.055526733398): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738547 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738547 AND published='1' LIMIT 1

109 (45.061111450195): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738547 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738547 AND published='1' LIMIT 1

110 (46.968460083008): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.id=294738547 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

111 (504.97055053711): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.id=294738547 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

112 (556.23054504395): SELECT dp.name, dp.id, dp2.name as channel, ex.name as author_name, ex.specialization, ex.images FROM jos_deeppockets as dp LEFT JOIN jos_experts as ex ON ex.id = dp.author LEFT JOIN jos_deeppockets as dp2 ON dp2.id = dp.fid WHERE dp.author != 0 AND dp.cat = 10 AND dp.published = 1 AND ( (dp.fid = 294743300) OR (dp.fid = 294743301) OR (dp.fid = 294743302) OR (dp.fid = 294743303) OR (dp.fid = 294743304) OR (dp.fid = 294743305) OR (dp.fid = 294743306) OR (dp.fid = 294743307) OR (dp.fid = 294743308) OR (dp.fid = 294743309) OR (dp.fid = 294743310) ) ORDER BY RAND() LIMIT 1

113 (369.07196044922): SELECT dp.name, dp.id, dp2.name as channel, ex.name as author_name, ex.specialization, ex.images FROM jos_deeppockets as dp LEFT JOIN jos_experts as ex ON ex.id = dp.author LEFT JOIN jos_deeppockets as dp2 ON dp2.id = dp.fid WHERE dp.author != 0 AND dp.cat = 10 AND dp.published = 1 AND ( (dp.fid = 294743300) OR (dp.fid = 294743301) OR (dp.fid = 294743302) OR (dp.fid = 294743303) OR (dp.fid = 294743304) OR (dp.fid = 294743305) OR (dp.fid = 294743306) OR (dp.fid = 294743307) OR (dp.fid = 294743308) OR (dp.fid = 294743309) OR (dp.fid = 294743310) ) ORDER BY RAND() LIMIT 1

114 (77.962875366211): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738547 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738547 AND published='1' LIMIT 1

115 (48.87580871582): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738547 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738547 AND published='1' LIMIT 1

116 (48.87580871582): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738547 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738547 AND published='1' LIMIT 1

117 (36.001205444336): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738547 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738547 AND published='1' LIMIT 1

118 (67.949295043945): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738547 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738547 AND published='1' LIMIT 1

119 (39.815902709961): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738547 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738547 AND published='1' LIMIT 1

120 (41.961669921875): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738547 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738547 AND published='1' LIMIT 1

121 (36.954879760742): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738547 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738547 AND published='1' LIMIT 1

122 (265.12145996094): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`

123 (!!!!! 19534.826278687): SELECT * FROM jos_deeppockets WHERE jos_deeppockets.cat = 10 AND jos_deeppockets.type = 'deeppockets_item' AND jos_deeppockets.published = 1 AND jos_deeppockets.created + INTERVAL 14 DAY >= NOW() ORDER BY jos_deeppockets.hits DESC LIMIT 7

124 (478.02925109863): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294738547 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294738547 AND type='deeppockets_item' AND published='1' LIMIT 1

125 (!!!!! 7273.9124298096): ( SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.video != '' AND dp.video_source != '' AND dp.cat = 10 AND dp.published = 1 AND dp.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) UNION ( SELECT dpa.id, dpa.name, dpa.title, dpa.video, dpa.video_source, dpa.created FROM jos_deeppockets_archive AS dpa WHERE dpa.video != '' AND dpa.video_source != '' AND dpa.cat = 10 AND dpa.published = 1 AND dpa.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) ORDER BY created DESC LIMIT 3

126 (77.009201049805): ( SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.video != '' AND dp.video_source != '' AND dp.cat = 10 AND dp.published = 1 AND dp.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) UNION ( SELECT dpa.id, dpa.name, dpa.title, dpa.video, dpa.video_source, dpa.created FROM jos_deeppockets_archive AS dpa WHERE dpa.video != '' AND dpa.video_source != '' AND dpa.cat = 10 AND dpa.published = 1 AND dpa.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) ORDER BY created DESC LIMIT 3

127 (46.014785766602): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803337 LIMIT 1

128 (30.994415283203): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803337 LIMIT 1

129 (37.908554077148): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803276 LIMIT 1

130 (30.040740966797): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803276 LIMIT 1

131 (312.08992004395): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets_archive AS dp WHERE dp.id = 294803276 LIMIT 1

132 (36.001205444336): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets_archive AS dp WHERE dp.id = 294803276 LIMIT 1

133 (30.994415283203): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294802958 LIMIT 1

134 (30.040740966797): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294802958 LIMIT 1

135 (499.01008605957): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738547 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

136 (350.9521484375): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738547 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

137 (39.100646972656): SELECT name FROM jos_deeppockets WHERE id=212

138 (29.087066650391): SELECT name FROM jos_deeppockets WHERE id=212

139 (594.13909912109): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))212((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3

140 (530.00450134277): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))212((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3

141 (77.009201049805): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738547 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738547 AND published='1' LIMIT 1

142 (44.822692871094): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738547 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738547 AND published='1' LIMIT 1

143 (!!!!! 10123.014450073): TRUNCATE TABLE jos_trademed_module

144 (113.01040649414): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294738547 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

145 (56.028366088867): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294738547 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

146 (757.93266296387): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738547 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

147 (58.889389038086): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738547 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

148 (!!!!! 2068.042755127): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738547 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738547 AND published='1' LIMIT 1

149 (94.175338745117): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738547 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738547 AND published='1' LIMIT 1

150 (!!!!! 1204.9674987793): SELECT jos_item.* FROM jos_item INNER JOIN jos_number ON jos_item.numberID=jos_number.id WHERE 1=1 AND (jos_item.imgMini<>'') AND jos_item.type='L' AND jos_item.numberID= ( SELECT jos_number.id FROM jos_number WHERE jos_number.journalID IN (10) and jos_number.id in (select distinct jos_number.id from jos_number join jos_item on jos_item.numberid=jos_number.id where jos_item.type='P') ORDER BY (CONVERT(SUBSTRING(issue,1,2),SIGNED) + (CONVERT(SUBSTRING(issue,3,2),SIGNED)*100)) DESC LIMIT 0,1 ) ORDER BY RAND() DESC LIMIT 6

151 (62.942504882812): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738547 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738547 AND published='1' LIMIT 1

152 (46.968460083008): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738547 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738547 AND published='1' LIMIT 1

153 (36.001205444336): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294738547 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294738547 AND type='deeppockets_item' AND published='1' LIMIT 1

154 (31.948089599609): select distinct links.* from jos_textlinks links join jos_textlinks_placement placement on links.id=placement.link_id where journal_id=(10) and (channel_id=212 or channel_id is null)

155 (30.040740966797): select distinct links.* from jos_textlinks links join jos_textlinks_placement placement on links.id=placement.link_id where journal_id=(10) and (channel_id=212 or channel_id is null)

156 (30.994415283203): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1

157 (138.99803161621): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738547 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738547 AND published='1' LIMIT 1

158 (96.08268737793): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738547 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738547 AND published='1' LIMIT 1

159 (!!!!! 1178.0261993408): select jos_twitters.link from jos_twitters where cat=10

160 (35.04753112793): select jos_facebook.link from jos_facebook where cat=10

161 (30.994415283203): select jos_google_plus.link from jos_google_plus where cat=10

162 (27.894973754883): select jos_linkedin.link from jos_linkedin where cat=10

163 (270.12825012207): update jos_bannersmanager_banner set impmade=impmade+1 where id in(14615,14202,14203)

164 (!!!!! 1286.9834899902): insert into jos_banners_delta values (14615,'2025-06-26 19:47:09','216.73.216.249','view'),(14202,'2025-06-26 19:47:09','216.73.216.249','view'),(14203,'2025-06-26 19:47:09','216.73.216.249','view')

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